#2019GM-OCT

[!INFO] Concordance
Concordance exists when all the QRS complexes in the chest leads are either predominantly positive or predominantly negative. Source
Concordance can be Positive or Negative.

• Positive concordance suggests that the VT focus is in the posterior ventricular wall
• Negative cocordance suggests that the VT focus is in the anterior ventricular wall
• i.e it corresponds to the overall direction of depolarization relative to the chest eleads.
• 

VT Vs. SVT

Source
ABCDE
In VT:

1. Axis will be north-west (-90 to 180)
2. Broad complxes
3. Condordant
4. D - dissociation (AV)
5. E - Early part of QRS
   1. Because VT depolarizations are initially conducted through the ventricular muscle (and then reach the conducting system), the initial part of QRS complex will be 'slow' -> i.e slurred.
   2. 

Spyhilis

#2019GM-OCT/Q27

Source

Treponema pallidum cannot be cultured:

Serology and CSF examination are the mainstays for diagnosis. VDRL (Venereal Disease Research Laboratory) and RPR (rapid plasma reagin) tests are nontreponemal tests used for screening for syphilis.

Tertiary syphilis manifestations

General paralysis of the insane

AKA paretic neurosyphilis, dementia paralytica

• Occurs 10 - 25 years after primary infection
• Progressive dementia
• CSF lymphocytosis occurs with elevated protein.
• CSF VDRL is reactive.

Tabes dorsalis

A disease of the posterior columns and the dorsal roots.
Physical examination of late neurosyphilis:

• Loss of deep tendon reflexes in lower limbs
• Argyll Robertson pupil [[2020-BasicSciences-July#^6ae35e]]
• Loss of joint positions sense and vibration (doral columns) and stamping gait. (tabetic gait)
• ataxia

Symptoms:

• The commonest two are
  • Sensory ataxia
  • Sudden severe stabbing back pain: lancinating pains (lasts minutes to days), can involve the face.
• Severe epigastric pain
• Urinary retension

Treatment

IV penicillin

^6ae35e

What teriparatide?

Teriparatide is a recombinant fragment of human parathyroid hormone consisting

Spongy bone = trabercular bone;
Compact bone = cortical bone.

Definitions

Basically a syndrome of weak bones. (increased fragility).
Low bone mass + 'micro-architectural deterioration' leading to enhanced bone fragility and fracture risk.
Bone density is measured at the hip and the spine.

• If Density is < -2.5 T score => Osteoporosis
• -1 to -2.5 => Osteopenia

Pathogenesis and risk factors

Loss of bone mass is due to

• decreased deposition by osteoblasts and
• increased reabsorption by osteoclasts

Risk factors for fragility fractures are BMD dependent or BMD-independent.
(? only the BMD dependent ones are risk factors for osteoporosis)

Major causes of low BMD explained:
Oestrogen deficiency

[!INFO] Oestrogen deficiency causes ⬆deposition & ⬆⬆⬆ resorption
Oestrogen AND androgen deficiency cause increased bone turover with increased osteoblastic deposition AND increased osteoblastic resorption but resorption >> deposition and this leads to overall loss of bone density.Source

Oestrogen deff also causes:

• Premature arrest of bone deposition
• Increased number of remodelling units.
• Oestrogen deficiency is a major factor in the producing accelerated bone loss. (Oestrogen deficieny can be cause by anorexia nervosa and in athletes)
• Sex hormones exert these effects by regulating the rate of formation and apoptosis of osteoblasts and osteoclasts.

Glucocorticoids

• Induce a high turnover state and then a low turnover state with gradual decline of density

Ageing

• Causes trabercularization of coritcal bone -> increased fragility

Diagnosis

[!INFO] The gold standard is DXA
It measures bone density per square aread, NOT per unit volume. Even so, it is very accurate.
Falsely high values can be produces by osteophytes in the elderly.

Management options

The goal of management is to prevent future fractures.
Therefore, whether to treat or not and treatment option used depend on the current fracture risk. This is determined by risk scores such as the FRAX score.

Strongest predictor for future fractures is a history of fragility fracture. (i.e you have one, you're likely to get another)

In USA, for example, 10 year hip fracture risk > 3% or major osteoporotic fracture risk > 20% are indications to start treatment.

Management of fractures

• Vertebral fratures require only analgesia rest and physiotherapy.

Prevention

• Lifelong Calcium and vitamin D supplementation.
• Weight bearing exercise
• Avoid smoking, reduce alcohol.
• Reduction of falls : physiotherapy and home safety.

Pharmacotherapy

All block resorption except teriparatide.

• First line options: Bisphosphonates and denosumab

[!INFO] Phamacologic options and efficacy

Raloxifene and Bazedoxifene prevent only vertebral fractures.

• They are rarely used to treat osteoporosis.
• Everything else works for both vertebral and non vertebral fractures.
• Hip fractures are not prevented by teriparatide and Ibandronate. (and also raloxifene and bazedoxifene)

[!TIP] Mnemonic:

Bisphophoates

Bind to bone hydroxyapetite and inhibit osteoclasts.

• Alendronate and risendronate - once weekly dose

• ibandronate - once monthly.

• Zoledronate - once yearly infusion

• Bisphophonates can be used in late CKD but with careful monitoring.

• beware! osteonecrosis of the jaw! -> occurs with HIGH dose IV bisphophonates.

• prolonged treatment itself can lead to atypical fractures -> treatment should probably be stopped if T score has improved above -2.5.

Denosumab

Human antibody against RANKL which causes decreased resorption. Given every 6 months. Prevents fractures at all sites. Few side effects. Can cause osteonecrosis of the jaw. Can cause dysuria.

Strontrium ranelate

rarely used due to cardiovascular and thromboembolic events.

Teriparatide

Synthetic PTH analog -> has a 'paradoxical' effect of decreasing resorption.

When under continuous exposure to PTH (e.g., hyperparathyroidism), bone undergoes resorption more than formation, while intermittent exposure to low-dose PTH (like daily administration of teriparatide) induces bone formation more than resorption. Source

It's a daily sub cut injection ; difficult to take.
Used for resistant osteoporosis and severe vertebral osteoporosis.
Contraindicated for fractures due to skeletal mets and osteosarcoma.

SERMS

[!TIP] SERMS: only for the spine
Rarely used to treat osteoposoris
Being 'selective', they don't act on the uterus.
They do act on bone and decrease resorption.
Site of action is tricky: They reduce fracture risk on at the vertebra but they do reduce resorption at both the hip and spine
Increased thromboembolic risk and flushing.

Calcitriol and calcitonin

Not evidence backed; not used.

Primaquine reduces transmisibility. Main action is to eradicate hyponozoites. Also acts against gametocytes but has no effect against asexual blood stages.
(i.e so it works against hypnozoites and gametocytes)